The prostaglandin paradox: Additive inhibition of neutrophil function by aspirin-like drugs and the prostaglandin E1 analog misoprostol

E. A. Kitsis, G. Weissmann, S. B. Abramson

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Nonsteroidal antiinflammatory drugs (NSAID) are thought to act in part by inhibiting prostaglandin H (PGH) synthase which diminishes release of inflammatory prostaglandins (PG). Paradoxically, PG of the E series also have antiinflammatory properties. We therefore studied the combined effects of NSAID and PGE1 on neutrophil activation. Incubation of neutrophils with a PGE1 analog, misoprostol (miso; 1 μM; 5 min, 37°), reduced superoxide anion generation in response to the chemoattractant fmet-leu-phe (FMLP) to 70.7 ± 7% of control (p < 0.01). Piroxicam (10 μM) independently reduced FMLP dependent superoxide anion generation to 63.7 ± 7.4% (p < 0.01) of control. Addition of miso to piroxicam reduced superoxide anion production to 37.4 ± 1.9%, an inhibition that exceeded that observed with either drug alone. Similarly, the addition of miso enhanced the inhibitory effects of indomethacin and sodium salicylate on superoxide anion generation, and of all 3 NSAID on other neutrophil functions (degranulation, aggregation and global rises in cytosolic calcium). Miso (1 μM) and NSAID, alone or in combination, did not inhibit superoxide anion generation in response to the calcium ionophore A23187 or phorbol myristate acetate, agents that bypass G protein depending signaling pathways, and that do not induce a rise in cytosolic cyclic AMP (cAMP). Therefore, our data clearly show that miso at micromolar concentrations, augments the inhibitory effects of NSAID on neutrophil activation via a mechanism dependent upon signal transduction across the plasma membrane.

Original languageEnglish (US)
Pages (from-to)1461-1465
Number of pages5
JournalJournal of Rheumatology
Volume18
Issue number10
StatePublished - 1991
Externally publishedYes

Keywords

  • NSAID
  • inflammation
  • misoprostol
  • neutrophil
  • prostaglandin

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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